Protective effects of a vitamin B12 analog, methylcobalamin, against glutamate cytotoxicity in cultured cortical neurons

Eur J Pharmacol. 1993 Sep 7;241(1):1-6. doi: 10.1016/0014-2999(93)90925-8.


The effects of methylcobalamin, a vitamin B12 analog, on glutamate-induced neurotoxicity were examined using cultured rat cortical neurons. Cell viability was markedly reduced by a brief exposure to glutamate followed by incubation with glutamate-free medium for 1 h. Glutamate cytotoxicity was prevented when the cultures were maintained in methylcobalamin-containing medium. Glutamate cytotoxicity was also prevented by chronic exposure to S-adenosylmethionine, which is formed in the metabolic pathway of methylcobalamin. Chronic exposure to methylcobalamin and S-adenosylmethionine also inhibited the cytotoxicity induced by N-methyl-D-aspartate or sodium nitroprusside that releases nitric oxide. In cultures maintained in a standard medium, glutamate cytotoxicity was not affected by adding methylcobalamin to the glutamate-containing medium. In contrast, acute exposure to MK-801, a NMDA receptor antagonist, prevented glutamate cytotoxicity. These results indicate that chronic exposure to methylcobalamin protects cortical neurons against NMDA receptor-mediated glutamate cytotoxicity.

MeSH terms

  • Animals
  • Cell Death / drug effects
  • Cells, Cultured
  • Cerebral Cortex / cytology
  • Cerebral Cortex / drug effects
  • Dizocilpine Maleate / pharmacology
  • Excitatory Amino Acid Antagonists*
  • Female
  • Glutamates / toxicity
  • Glutamic Acid
  • N-Methylaspartate / antagonists & inhibitors
  • N-Methylaspartate / toxicity
  • Neurons / drug effects*
  • Neurotransmitter Agents / antagonists & inhibitors*
  • Neurotransmitter Agents / toxicity
  • Nitroprusside / pharmacology
  • Pregnancy
  • Rats
  • S-Adenosylmethionine / pharmacology
  • Vitamin B 12 / analogs & derivatives*
  • Vitamin B 12 / pharmacology


  • Excitatory Amino Acid Antagonists
  • Glutamates
  • Neurotransmitter Agents
  • Nitroprusside
  • Glutamic Acid
  • N-Methylaspartate
  • Dizocilpine Maleate
  • S-Adenosylmethionine
  • mecobalamin
  • Vitamin B 12